The creation of channels in a substrate at a microminiaturized scale has many potential applications. When suitably enclosed so as to confine the motion of a fluid to the channel, these structures may be used to provide a well-defined flow path for liquids or gases. Microchannels serve a wide variety of purposes, ranging from mere routing of fluid flow from a source to a destination or partitioning of a source volume into multiple streams; to mixing of two or more fluids for purposes of dilution, multi-phase extraction, or reaction; to chemico-physical interaction of the channeled fluid with physical structures created in the channel, e.g., for chromatographic separation; to analysis of fluid components by means of optical probing and other detection techniques.
Academic and commercial efforts to develop and manufacture fluidic channel devices and systems have utilized a variety of materials. The choice of materials has been dictated by performance requirements of the finished devices, by available processing equipment, and by individually established experience and familiarity with certain materials. A large body of published research details work on silicon, quartz, glass and plastic substrates.
Much early work was done with glass substrates or slides, generally for reasons of familiarity and compatibility with extant detection systems, or of ability to electrically insulate voltages ranging up to 10 kV in electrokinetically-driven separations.
Quartz substrates have also been used for fabrication of microchannel-based devices and systems, despite difficulties in processing due to the material's hardness and relative inertness.
Due to economically attractive materials costs, a variety of plastics have been considered and evaluated as substrate materials for microchannels. Although incompatibility with fluidic constituents can limit choice of specific materials due to possible contamination of transported fluids, the relatively inexpensive cost of plastics vis-a-vis glass or silicon substrates has driven continued work for certain applications.
Silicon has been regarded as a potentially valuable substrate for a wide variety of microelectromechanical applications for several decades. The relatively recent growth of interest in silicon as a substrate for microfluidic devices and systems is, in part, attributable to the emergence of process equipment that is suitable for fabricating structures with better-defined architectures and high aspect ratios.
Shallow channels may be formed from any of these materials. Shallow channels typically may be fabricated having dimensions from 1 to 100 μm in width, 1 to 100 μm in depth, and 10 μm to 10 mm in length. These dimensions correspond to a cross-sectional area of 1 to 104 μm2 and total contained fluid quantities of 101 to 108 μm3, or 10 fL to 100 nL.
These dimensions offer the advantages of reduced fluid volume over macro systems. Very small quantities of fluids are needed to fill microchannels and, conversely, very small quantities of effluent fluid are produced. This constitutes a principal attraction of these structures.
Shallow channels also offer performance advantages: undesired dead volume originating from separate component interconnection can be significantly reduced or eliminated; operation time can be greatly lessened due to shortened fluid flow path lengths; more effective separations can be done due to increased surface-to-volume ratios; and greatly reduced quantities of solvents and reagents are required (with concomitant reduction of effluent volumes), as discussed previously.
Fabrication methods and equipment developed for the creation of standard semiconductor industry products like microprocessors, memory, and logic, and later used for the manufacturing of microelectromechanical systems (MEMS), are particularly well-suited for use in the creation of microfluidic channels in silicon. The art of creating intricate, multi-layer patterns in silicon and compatible materials through deposition, lithographic, and etching processes is extremely well developed and reproducible in those industries.
Dry etching of silicon, whether primarily physical in nature (ion-milling) or primarily chemical (plasma etching), is a highly evolved part of the overall MEMS fabrication process. Reactive-ion etching (RIE) is a method of etching that is a combination of physical and chemical mechanisms, and is the most commonly practiced embodiment of dry etching. RIE, through judicious selection and optimization of reactant gases, pressure, temperature, and power sources, can attain both a high degree of anisotropy as well as good selectivity (differentiation among unlike materials). A particular class of silicon etch processes has been considered specifically for high-aspect-ratio etching of silicon in MEMS applications.
Confinement of fluids to channels is an indispensable requirement for controlled operation of microfluidic devices and systems. Although three of the required four sides in a channel of rectangular cross-section may be formed as a natural consequence of the etching processes, the remaining side must be provided through additional process steps. There are a variety of methods by which a lid substrate may be attached to a channel substrate, including anodic bonding, fusion bonding, frit bonding, and attachment through the use of “glue” layers, generally organic in nature. Anodic bonding, when suitable for a given device and application, provides a strong, hermetic bond between a silicon substrate and a glass lid substrate.
Simple microfluidic systems may be enhanced by defining additional functionality in the fluidic device. The functionality defined may include electrospray ionization (ESI), liquid chromatography (LC), and integrated LC/ESI devices and systems. The additional functionality may be as simple as electrical contacts for purposes of effecting electrokinetic flow and separation in the channels. On the other hand, the incremental functionality may take the form of additional microstructures, such as nozzles for purposes of electrospray to transport fluids off-chip. Creation of the desired functionality can be commonly achieved by integration of appropriate additional patterns in design and layout as well as additional process operations. This offers a significant advantage over a system built by macroscopic assembly of individual components.
Other researchers have similarly considered microfluidic systems in which the basic functionality of microfluidic channels was enhanced through the creation of intra-channel structures.
Although device design for microfluidic applications entails consideration of often-challenging constraints that go beyond the basic creation of the microfluidic channels themselves, the fabrication of channels with dimensions of a micron or more as discussed above is generally straightforward.
Many applications have been identified and more are anticipated for channels that have been etched into a substrate such as silicon, glass, quartz, or fused silica with depth of channels typically ranging from 10 to 100 μm in depth. Such channels can be fabricated using known techniques. New applications are emerging, however, for channels that are 1/10– 1/1000 of those depths, i.e., depths ranging from approximately 10 to 1000 nm (“ultra-shallow channels”). Applications for ultra-shallow channels often require more precise tolerances than standard devices, thus increasing the fabrication challenge.
The typical etch processes described above are not capable of producing devices to such specification. RIE, for example, etches at rates that make sub-micron control difficult in any dimension. Also, whereas lateral dimensions are more easily varied (at least for critical dimensions greater than 1 μm) through layout in CAD, vertical differentiation of features (e.g., controllably varied channel depths) can be very difficult to achieve in currently-practiced processing schemes, and cannot be controlled at all reliably with sub-micron precision.
Fabrication of ultra-shallow channels is difficult to achieve with sufficient control for reproducibility in manufacturing. Standard etch processes and equipment are generally designed to maximize etch rate while maintaining at least a minimal level of other performance parameters like selectivity to masking materials. In the case of ultra-shallow channels, however, low etch rates are needed so as to afford an acceptable degree of precision. That is, in the absence of a detectable and definitive endpoint, etch depth is determined by etch time, given an established etch rate. For example, with a typical RIE etch rate of several micrometers per minute, a 50 nm channel would nominally require an etch time of only 1–2 seconds. Since there are transient plasma conditions after ignition that last several seconds during which etch rates and uniformities are not characteristic of the stabilized etch process, reproducibility of an etch of a few seconds duration is unachievable, and etch durations of less than two seconds produce inherently unreliable results.
There is a need for devices having ultra-shallow channels. Ultra-shallow channel devices meet some of the following requirements: minimizing fluid volume; maximizing interaction with channel surfaces (high surface-to-volume ratio); controlling the flow of a transported fluid in the laminar or molecular flow regime; acting as a filter for particles of greater dimension than the channel depth; and increasing the signal-to-noise (S/N) ratio for optical probing techniques by limiting the required depth of field in optical detection systems and other factors. Current state of the art processes cannot produce devices incorporating ultra-shallow channels reliably or repeatably.